Journal article
Sequence alignment reveals possible MAPK docking motifs on HIV proteins
PloS one, v 5(1), pp e8942-e8942
28 Jan 2010
PMID: 20126615
Featured in Collection : UN Sustainable Development Goals @ Drexel
Abstract
Over the course of HIV infection, virus replication is facilitated by the phosphorylation of HIV proteins by human ERK1 and ERK2 mitogen-activated protein kinases (MAPKs). MAPKs are known to phosphorylate their substrates by first binding with them at a docking site. Docking site interactions could be viable drug targets because the sequences guiding them are more specific than phosphorylation consensus sites. In this study we use multiple bioinformatics tools to discover candidate MAPK docking site motifs on HIV proteins known to be phosphorylated by MAPKs, and we discuss the possibility of targeting docking sites with drugs. Using sequence alignments of HIV proteins of different subtypes, we show that MAPK docking patterns previously described for human proteins appear on the HIV matrix, Tat, and Vif proteins in a strain dependent manner, but are absent from HIV Rev and appear on all HIV Nef strains. We revise the regular expressions of previously annotated MAPK docking patterns in order to provide a subtype independent motif that annotates all HIV proteins. One revision is based on a documented human variant of one of the substrate docking motifs, and the other reduces the number of required basic amino acids in the standard docking motifs from two to one. The proposed patterns are shown to be consistent with in silico docking between ERK1 and the HIV matrix protein. The motif usage on HIV proteins is sufficiently different from human proteins in amino acid sequence similarity to allow for HIV specific targeting using small-molecule drugs.
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Details
- Title
- Sequence alignment reveals possible MAPK docking motifs on HIV proteins
- Creators
- Perry Evans - Genomics and Computational Biology and Department of Computer and Information Science, University of Pennsylvania, Philadelphia, Pennsylvania, United States of AmericaAhmet SacanLyle UngarAydin Tozeren
- Publication Details
- PloS one, v 5(1), pp e8942-e8942
- Publisher
- Public LIbrary of Science (PLOS); United States
- Grant note
- #232240 / PHS HHS T32 HG000046 / NHGRI NIH HHS
- Resource Type
- Journal article
- Language
- English
- Academic Unit
- School of Biomedical Engineering, Science, and Health Systems; [Retired Faculty]
- Web of Science ID
- WOS:000274138000019
- Scopus ID
- 2-s2.0-77952538851
- Other Identifier
- 991014877685304721
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- Collaboration types
- Domestic collaboration
- Web of Science research areas
- Biochemistry & Molecular Biology